Design, synthesis, and biological evaluation of new cyclic melanotropin peptide analogues selective for the human melanocortin-4 receptor.

ABSTRACT: Intensive efforts have been made to develop potent and selective ligands for certain human melanocortin receptors as possible treatments for obesity and sexual dysfunction due to the role of these receptors in feeding behavior, energy homeostasis, sexual function, etc. A number of novel alpha-MSH analogues were designed and synthesized primarily on the basis of our previous MTII NMR structure. In these peptide analogues, a disulfide or lactam bridge between residues at positions 5 and 8 was used as a conformational constraint to enhance the beta-turn spanning His6 and D-Phe7, while the pharmacophore group in Arg8 was mimicked via Nalpha-alkylation of residues 8 or 9 with the guanidinylbutyl group. Biological assays for binding affinities and adenylate cyclase activities for the hMC1R, hMC3

SUBMITTER: Ying J 

PROVIDER: S-EPMC1764620 | biostudies-literature | 2006 Nov

REPOSITORIES: biostudies-literature